During the course of a viral infection, viral proteins interact with an array of host proteins and pathways. Here, we present a systematic strategy to elucidate the dynamic interactions between H1N1 influenza and its human host...

..These efforts have already translated into the identification of novel antiviral targets and the development of new therapeutic strategies, some of which are currently undergoing clinical evaluation...

An efficient recombination system for chromosome engineering in Escherichia coli

..Serological studies showed that by the age of five years, virtually all children in the Netherlands have been exposed to human metapneumovirus and that the virus has been circulating in humans for at least 50 years...

..We also resolved many of the past taxonomic problems by establishing phylogenetic relationships of the antigenically unclassified viruses with the well-established viruses and by identifying synonymous viruses...

..We conclude that interactions between NS2 and E1 and p7 as well as between NS2 and NS3 are essential for virus assembly and/or release and that each of these viral proteins plays an important role in this process.

The PB2 subunit of the influenza virus RNA polymerase affects virulence by interacting with the mitochondrial antiviral signaling protein and inhibiting expression of beta interferon

..Overall this study implicates the PB2 protein in the regulation of host antiviral innate immune pathways and suggests an important role for the mitochondrial association of the PB2 protein in determining virulence...

Identification of amino acids in HA and PB2 critical for the transmission of H5N1 avian influenza viruses in a mammalian host

..The protease domain of NS2 was required for infectivity, whereas its catalytic active site was dispensable. We conclude that p7 and NS2 function at an early stage of virion morphogenesis, prior to the assembly of infectious virus...

Helen M WiseDepartment of Pathology, University of Cambridge, United KingdomJ Virol 83:8021-31. 2009

..Thus, the influenza A virus proteome includes a 12th primary translation product that (similarly to PB1-F2) is nonessential for virus viability but whose loss, in particular genetic backgrounds, is detrimental to virus replication...

..Despite such ubiquity, the link between EBV and 'endemic' Burkitt's lymphoma proved consistent and became the first of an unexpectedly wide range of associations discovered between this virus and tumours...

..Virchows Arch. B., 33:233-243, 1980). In view of this finding and the observation that all HCV proteins accumulate on the membranous web, we propose that the membranous web forms the viral replication complex in HCV-infected cells...

Concurrent expression of latent and a limited number of lytic genes with immune modulation and antiapoptotic function by Kaposi's sarcoma-associated herpesvirus early during infection of primary endothelial and fibroblast cells and subsequent decline of l

..Thus, DAI interacts with RIP3 to mediate virus-induced necrosis analogous to the RIP1-RIP3 complex controlling death receptor-induced necroptosis. These studies unveil a role for DAI as the RIP3 partner mediating virus-induced necrosis...

Failure to activate the IFN-β promoter by a paramyxovirus lacking an interferon antagonist

..Since domain III of NS5A is one of the most variable regions in the HCV genome, the results suggest that viral isolates may differ in their level of virion production and thus in their level of fitness and pathogenesis...

..Here, we summarize the current knowledge on the viral modulation of mitochondrial apoptosis, by focusing in particular on the mechanisms by which viral proteins control the host cell death apparatus.

..Moreover, the observation that p19-expressing transgenic plants show altered leaf morphology might indicate that the p19-targeted PTGS pathway is also important in the regulation of plant development...

..However, the order of these changes differed between replicates, and parallel substitutions did not reflect the changes with the largest beneficial effects or indicate a common trajectory of adaptation...

Identification of amino acid residues critical for the anti-interferon activity of the nucleoprotein of the prototypic arenavirus lymphocytic choriomeningitis virus

Luis Martinez-SobridoDepartment of Immunology, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, New York 10029, USAJ Virol 83:11330-40. 2009

..In addition, A549 cells infected with rLCMV/NP*(D382A), but not with WT LCMV, produced IFN and failed to rescue replication of the IFN-sensitive Newcastle disease virus...

Interaction of polymerase subunit PB2 and NP with importin alpha1 is a determinant of host range of influenza A virus

..These results strongly suggest that PML functions as part of an intrinsic immune mechanism against cytomegalovirus infections...

The influenza virus protein PB1-F2 inhibits the induction of type I interferon at the level of the MAVS adaptor protein

Zsuzsanna T VargaDepartment of Microbiology, Mount Sinai School of Medicine, New York City, New York, United States of AmericaPLoS Pathog 7:e1002067. 2011

..In summary, we have characterized the anti-interferon function of PB1-F2 and we suggest that this activity contributes to the enhanced pathogenicity seen with PB1-F2 N66S- expressing influenza viruses...

Characterization of the human cytomegalovirus gH/gL/UL128-131 complex that mediates entry into epithelial and endothelial cells

E C HutchinsonSir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United KingdomVaccine 30:7353-8. 2012

..In this review we discuss how the virus exploits nuclear import pathways to allow regulated and chaperoned assembly of RNPs in the nucleus, and describe how the import machinery itself can be a determinant of host tropism...

The phage lambda major tail protein structure reveals a common evolution for long-tailed phages and the type VI bacterial secretion system

..Macrophages and dendritic cells (DC) in mucosal tissues express receptors that are triggered by viral proteins and nucleic acids, leading to the secretion of anti-viral factors that destroy the invading pathogen...

..events in cell fusion via post-translational modifications of tyrosine and/r lysine residues by cellular or viral proteins. Mass spectrometry will be used to identify cellular and viral proteins that interact with the gBcyt domain in ..

..the unique advantage of targeting receptor-ligand interactions that are completely independent of mutable viral proteins. A similar delivery system targeting Glycoprotein D of herpes simplex type 2 will also prevent infection with ..

..2) With affinity pull-down and mass spectrometry we will identify the putative viral proteins of 55, 38, and 22 kDa that UV-crosslink to stem-loop III and nine abundant cellular proteins that UV-crosslink ..

..Thus, lower MBL expression or function can result in neuroinflammation and anomalous accumulation of viral proteins and immune complexes in brain leading to neurotoxicity and neurocognitive impairment...

..We will define the mechanism of tetherin inhibition and determine if tetherin is antagonized by 6K or other viral proteins. We will determine the activity of 6K in directly modulating membrane curvature at the bud site. 3...

..detection and clearance by several mechanisms including the ability to reversibly down-regulate immunogenic viral proteins. This down-regulation is known to be regulated by epigenetic changes in the latent viral chromosome...

..latter complexes either function as competitors for SG formation and/or serve in the preferential synthesis of viral proteins. The proposed research plan is focused on two broad Specific Aims: i) to study virus-specific protein ..

..steps in development of an innovative new global high-throughput assay approach for identifying and measuring viral proteins as targets for humoral (neutralizing antibodies) and T-cell-mediated immune responses to KSHV and other human ..

..with HIV is associated with a variety of neurological impairments that result from the presence of the viral proteins. HIV-1 trans-activator of transcription (Tat) protein is essential for efficient viral replication and plays a ..

..The senescence phenotype can be circumvented by expression of oncogenic viral proteins as well as by exposure to specific cytokines, suggesting pathways for malignant transformation in the setting ..

..group from UC, we will examine the epigenetic effects of exposure of a human beta cell line to HCV viral proteins or infectious virions, as well as the epigenetic modifications induce by IFNa in human beta cells...

..that involves dysregulation of immunomodulators and cytokines, and their downstream signaling pathways by viral proteins, such as gp120 and Tat, in both infected and uninfected bystander cells including neurons...

..We will use cell-free studies to determine how cellular cyclophilin proteins interact with two viral proteins NS5A and NS5B and how viral protein interactions differ depending upon whether they are from strains of HCV ..

..the first aim, intra-neuronal spread of measles virus to the synapse is studied, which will characterize the viral proteins that are present at synaptic membranes, and whether these proteins are required for trans-synaptic spread...

..The ORF encodes a large polypeptide that is processed to structural and nonstructural viral proteins. The roles of viral proteins and conserved RNA sequences/structures in HCV replication are poorly understood...

This project will test the hypothesis that mapping the viral RNA and characterizing the early viral proteins of human papillomavirus (HPV) will improve our understanding of how these viruses alter the normal keratinocyte and how this may ..